IL301950A - HMPV F proteins are pre-stabilized - Google Patents

Info

Publication number

IL301950A

IL301950A IL301950A IL30195023A IL301950A IL 301950 A IL301950 A IL 301950A IL 301950 A IL301950 A IL 301950A IL 30195023 A IL30195023 A IL 30195023A IL 301950 A IL301950 A IL 301950A

Authority

IL

Israel

Prior art keywords

engineered

engineered protein

protein

substitution

seq

Prior art date

2020-10-09

Links

• Espacenet
• Global Dossier
• Discuss

• 108090000623 proteins and genes Proteins 0.000 title claims description 354
• 102000004169 proteins and genes Human genes 0.000 title claims description 334
• 235000018102 proteins Nutrition 0.000 claims description 314
• 238000006467 substitution reaction Methods 0.000 claims description 235
• 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 claims description 92
• 238000000034 method Methods 0.000 claims description 54
• 150000007523 nucleic acids Chemical class 0.000 claims description 53
• 102000039446 nucleic acids Human genes 0.000 claims description 49
• 108020004707 nucleic acids Proteins 0.000 claims description 49
• 239000013638 trimer Substances 0.000 claims description 49
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 46
• 241000351643 Metapneumovirus Species 0.000 claims description 39
• 235000018417 cysteine Nutrition 0.000 claims description 39
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 39
• 150000001413 amino acids Chemical class 0.000 claims description 38
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 38
• 239000000203 mixture Substances 0.000 claims description 37
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 33
• 229920001184 polypeptide Polymers 0.000 claims description 32
• 235000001014 amino acid Nutrition 0.000 claims description 31
• 108020004414 DNA Proteins 0.000 claims description 30
• 239000008194 pharmaceutical composition Substances 0.000 claims description 26
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 24
• 230000035772 mutation Effects 0.000 claims description 23
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 22
• 238000011049 filling Methods 0.000 claims description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
• 125000003729 nucleotide group Chemical group 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 16
• 239000002773 nucleotide Substances 0.000 claims description 14
• 238000005829 trimerization reaction Methods 0.000 claims description 13
• 208000015181 infectious disease Diseases 0.000 claims description 10
• 102220288073 rs151218932 Human genes 0.000 claims description 10
• 239000013604 expression vector Substances 0.000 claims description 9
• 108010076504 Protein Sorting Signals Proteins 0.000 claims description 8
• 238000011282 treatment Methods 0.000 claims description 8
• 206010066226 Metapneumovirus infection Diseases 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 108020004999 messenger RNA Proteins 0.000 claims description 7
• 102220514958 Vacuolar protein sorting-associated protein 4B_L66D_mutation Human genes 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 102200114233 rs797045190 Human genes 0.000 claims description 5
• 239000002671 adjuvant Substances 0.000 claims description 4
• 102220416308 c.139G>A Human genes 0.000 claims description 4
• 230000009881 electrostatic interaction Effects 0.000 claims description 4
• 102220193243 rs1057516148 Human genes 0.000 claims description 4
• 239000004261 Ascorbyl stearate Substances 0.000 claims description 3
• 239000013639 protein trimer Substances 0.000 claims description 3
• 102220123717 rs759057581 Human genes 0.000 claims description 3
• 102220240346 rs764757062 Human genes 0.000 claims description 3
• 102200026938 rs80356668 Human genes 0.000 claims description 3
• 230000035945 sensitivity Effects 0.000 claims description 3
• 125000003275 alpha amino acid group Chemical group 0.000 claims 4
• 241000342334 Human metapneumovirus Species 0.000 description 127
• 230000027455 binding Effects 0.000 description 67
• 210000004027 cell Anatomy 0.000 description 67
• 239000000427 antigen Substances 0.000 description 66
• 102000036639 antigens Human genes 0.000 description 66
• 108091007433 antigens Proteins 0.000 description 66
• 230000014509 gene expression Effects 0.000 description 60
• 150000002632 lipids Chemical class 0.000 description 32
• 235000000346 sugar Nutrition 0.000 description 27
• 241000725643 Respiratory syncytial virus Species 0.000 description 24
• 230000004927 fusion Effects 0.000 description 24
• 235000002639 sodium chloride Nutrition 0.000 description 24
• 239000013598 vector Substances 0.000 description 24
• 239000012634 fragment Substances 0.000 description 23
• 238000013461 design Methods 0.000 description 22
• 238000001514 detection method Methods 0.000 description 21
• 229960005486 vaccine Drugs 0.000 description 21
• 239000000523 sample Substances 0.000 description 20
• 241000701161 unidentified adenovirus Species 0.000 description 20
• 102000025171 antigen binding proteins Human genes 0.000 description 19
• 108091000831 antigen binding proteins Proteins 0.000 description 19
• 230000001965 increasing effect Effects 0.000 description 19
• 239000003446 ligand Substances 0.000 description 19
• 239000012528 membrane Substances 0.000 description 19
• 229920001223 polyethylene glycol Polymers 0.000 description 19
• 238000001542 size-exclusion chromatography Methods 0.000 description 18
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 17
• 235000013930 proline Nutrition 0.000 description 17
• 241000700605 Viruses Species 0.000 description 16
• -1 azido, thio Chemical group 0.000 description 16
• 239000000243 solution Substances 0.000 description 16
• 210000001519 tissue Anatomy 0.000 description 16
• 238000004458 analytical method Methods 0.000 description 15
• 230000004048 modification Effects 0.000 description 15
• 238000012986 modification Methods 0.000 description 15
• 238000002965 ELISA Methods 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
• 238000003556 assay Methods 0.000 description 13
• 230000003472 neutralizing effect Effects 0.000 description 13
• 230000003612 virological effect Effects 0.000 description 13
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 12
• 230000002209 hydrophobic effect Effects 0.000 description 12
• 239000002105 nanoparticle Substances 0.000 description 12
• 229920000642 polymer Polymers 0.000 description 12
• 230000000890 antigenic effect Effects 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 239000013078 crystal Substances 0.000 description 11
• 238000011161 development Methods 0.000 description 11
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
• 239000003623 enhancer Substances 0.000 description 11
• 239000002777 nucleoside Substances 0.000 description 11
• 239000002953 phosphate buffered saline Substances 0.000 description 11
• 238000013459 approach Methods 0.000 description 10
• 125000002091 cationic group Chemical group 0.000 description 10
• 230000006870 function Effects 0.000 description 10
• 108020001507 fusion proteins Proteins 0.000 description 10
• 102000037865 fusion proteins Human genes 0.000 description 10
• 239000000499 gel Substances 0.000 description 10
• 238000011534 incubation Methods 0.000 description 10
• 238000005406 washing Methods 0.000 description 10
• 108091026890 Coding region Proteins 0.000 description 9
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 9
• 239000000872 buffer Substances 0.000 description 9
• 239000011159 matrix material Substances 0.000 description 9
• 102000040430 polynucleotide Human genes 0.000 description 9
• 108091033319 polynucleotide Proteins 0.000 description 9
• 239000002157 polynucleotide Substances 0.000 description 9
• 108010059722 Viral Fusion Proteins Proteins 0.000 description 8
• 230000009286 beneficial effect Effects 0.000 description 8
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 8
• 238000001415 gene therapy Methods 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 125000003835 nucleoside group Chemical group 0.000 description 8
• 239000002245 particle Substances 0.000 description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
• 238000003127 radioimmunoassay Methods 0.000 description 8
• 230000010076 replication Effects 0.000 description 8
• 150000003839 salts Chemical class 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• 150000003431 steroids Chemical class 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• 238000013518 transcription Methods 0.000 description 8
• 230000035897 transcription Effects 0.000 description 8
• 241000282412 Homo Species 0.000 description 7
• 108091028043 Nucleic acid sequence Proteins 0.000 description 7
• 125000000217 alkyl group Chemical group 0.000 description 7
• 238000003776 cleavage reaction Methods 0.000 description 7
• 150000001875 compounds Chemical class 0.000 description 7
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 230000002068 genetic effect Effects 0.000 description 7
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 7
• 230000005847 immunogenicity Effects 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 230000007017 scission Effects 0.000 description 7
• 239000007787 solid Substances 0.000 description 7
• 239000007790 solid phase Substances 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• 230000007704 transition Effects 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• 102000053602 DNA Human genes 0.000 description 6
• 102000004961 Furin Human genes 0.000 description 6
• 108090001126 Furin Proteins 0.000 description 6
• 102000003886 Glycoproteins Human genes 0.000 description 6
• 108090000288 Glycoproteins Proteins 0.000 description 6
• 238000007792 addition Methods 0.000 description 6
• 125000003342 alkenyl group Chemical group 0.000 description 6
• 230000003321 amplification Effects 0.000 description 6
• 229960002685 biotin Drugs 0.000 description 6
• 235000020958 biotin Nutrition 0.000 description 6
• 239000011616 biotin Substances 0.000 description 6
• 238000004422 calculation algorithm Methods 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 230000003247 decreasing effect Effects 0.000 description 6
• 238000002022 differential scanning fluorescence spectroscopy Methods 0.000 description 6
• 230000001976 improved effect Effects 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 238000003199 nucleic acid amplification method Methods 0.000 description 6
• 150000003904 phospholipids Chemical class 0.000 description 6
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 6
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
• UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 5
• 108020004705 Codon Proteins 0.000 description 5
• UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 108091034117 Oligonucleotide Proteins 0.000 description 5
• 241000711904 Pneumoviridae Species 0.000 description 5
• 102000002067 Protein Subunits Human genes 0.000 description 5
• 108010001267 Protein Subunits Proteins 0.000 description 5
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 210000004899 c-terminal region Anatomy 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 239000011248 coating agent Substances 0.000 description 5
• 238000000576 coating method Methods 0.000 description 5
• UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 5
• 238000012217 deletion Methods 0.000 description 5
• 230000037430 deletion Effects 0.000 description 5
• 238000002050 diffraction method Methods 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 229940088598 enzyme Drugs 0.000 description 5
• 230000028993 immune response Effects 0.000 description 5
• 230000000977 initiatory effect Effects 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 230000014759 maintenance of location Effects 0.000 description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
• 238000002439 negative-stain electron microscopy Methods 0.000 description 5
• 150000003833 nucleoside derivatives Chemical class 0.000 description 5
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 5
• 230000000717 retained effect Effects 0.000 description 5
• 241000894007 species Species 0.000 description 5
• 230000006641 stabilisation Effects 0.000 description 5
• 238000011105 stabilization Methods 0.000 description 5
• 230000000087 stabilizing effect Effects 0.000 description 5
• 238000001262 western blot Methods 0.000 description 5
• PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 4
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
• 230000004543 DNA replication Effects 0.000 description 4
• 241000702421 Dependoparvovirus Species 0.000 description 4
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
• 101710154606 Hemagglutinin Proteins 0.000 description 4
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 4
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
• 229930195725 Mannitol Natural products 0.000 description 4
• 239000000020 Nitrocellulose Substances 0.000 description 4
• 101710093908 Outer capsid protein VP4 Proteins 0.000 description 4
• 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 4
• 101710176177 Protein A56 Proteins 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
• 239000012472 biological sample Substances 0.000 description 4
• 229940098773 bovine serum albumin Drugs 0.000 description 4
• 239000011575 calcium Substances 0.000 description 4
• 150000001720 carbohydrates Chemical class 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 238000004590 computer program Methods 0.000 description 4
• 238000005520 cutting process Methods 0.000 description 4
• 229940104302 cytosine Drugs 0.000 description 4
• 230000001747 exhibiting effect Effects 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 238000000684 flow cytometry Methods 0.000 description 4
• 210000002443 helper t lymphocyte Anatomy 0.000 description 4
• 239000000185 hemagglutinin Substances 0.000 description 4
• 230000003053 immunization Effects 0.000 description 4
• 238000002649 immunization Methods 0.000 description 4
• 238000003364 immunohistochemistry Methods 0.000 description 4
• 206010022000 influenza Diseases 0.000 description 4
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
• 230000010354 integration Effects 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 230000000670 limiting effect Effects 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000000594 mannitol Substances 0.000 description 4
• 235000010355 mannitol Nutrition 0.000 description 4
• 238000002844 melting Methods 0.000 description 4
• 230000008018 melting Effects 0.000 description 4
• HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 4
• 230000007935 neutral effect Effects 0.000 description 4
• 229920001220 nitrocellulos Polymers 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 230000008488 polyadenylation Effects 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 238000012545 processing Methods 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• 238000001890 transfection Methods 0.000 description 4
• 229940035893 uracil Drugs 0.000 description 4
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
• 229930024421 Adenine Natural products 0.000 description 3
• 229920001817 Agar Polymers 0.000 description 3
• 108091028732 Concatemer Proteins 0.000 description 3
• 241000701022 Cytomegalovirus Species 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 108700026244 Open Reading Frames Proteins 0.000 description 3
• 241000711902 Pneumovirus Species 0.000 description 3
• 229920002873 Polyethylenimine Polymers 0.000 description 3
• 229920001213 Polysorbate 20 Polymers 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• 108010090804 Streptavidin Proteins 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 108020005202 Viral DNA Proteins 0.000 description 3
• 108010067390 Viral Proteins Proteins 0.000 description 3
• 229960000643 adenine Drugs 0.000 description 3
• 239000008272 agar Substances 0.000 description 3
• 125000000304 alkynyl group Chemical group 0.000 description 3
• 230000001580 bacterial effect Effects 0.000 description 3
• 238000012575 bio-layer interferometry Methods 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 230000001413 cellular effect Effects 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• 238000004891 communication Methods 0.000 description 3
• 230000000295 complement effect Effects 0.000 description 3
• 229920001577 copolymer Polymers 0.000 description 3
• 238000002447 crystallographic data Methods 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 210000002919 epithelial cell Anatomy 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 210000003128 head Anatomy 0.000 description 3
• 125000001165 hydrophobic group Chemical group 0.000 description 3
• 238000003018 immunoassay Methods 0.000 description 3
• 230000006872 improvement Effects 0.000 description 3
• 230000001939 inductive effect Effects 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• 238000007918 intramuscular administration Methods 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 125000005647 linker group Chemical group 0.000 description 3
• 230000007774 longterm Effects 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 230000034217 membrane fusion Effects 0.000 description 3
• 230000008520 organization Effects 0.000 description 3
• 229910052760 oxygen Inorganic materials 0.000 description 3
• 238000004806 packaging method and process Methods 0.000 description 3
• 244000052769 pathogen Species 0.000 description 3
• 239000013612 plasmid Substances 0.000 description 3
• 239000004033 plastic Substances 0.000 description 3
• 229920003023 plastic Polymers 0.000 description 3
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
• 229920000136 polysorbate Polymers 0.000 description 3
• 239000011591 potassium Substances 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 230000009870 specific binding Effects 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 150000008163 sugars Chemical class 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 230000008685 targeting Effects 0.000 description 3
• 229940113082 thymine Drugs 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
• 241001430294 unidentified retrovirus Species 0.000 description 3
• 229940125575 vaccine candidate Drugs 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• 210000003501 vero cell Anatomy 0.000 description 3
• 238000009736 wetting Methods 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
• OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 2
• RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 description 2
• HCGHYQLFMPXSDU-UHFFFAOYSA-N 7-methyladenine Chemical compound C1=NC(N)=C2N(C)C=NC2=N1 HCGHYQLFMPXSDU-UHFFFAOYSA-N 0.000 description 2
• UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
• MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 2
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
• 239000013607 AAV vector Substances 0.000 description 2
• 206010001258 Adenoviral infections Diseases 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 2
• 108090001008 Avidin Proteins 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 108090000565 Capsid Proteins Proteins 0.000 description 2
• 102100023321 Ceruloplasmin Human genes 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• 102000020897 Formins Human genes 0.000 description 2
• 108091022623 Formins Proteins 0.000 description 2
• BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 description 2
• 102000002265 Human Growth Hormone Human genes 0.000 description 2
• 241001135569 Human adenovirus 5 Species 0.000 description 2
• 241000725303 Human immunodeficiency virus Species 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• 108060003951 Immunoglobulin Proteins 0.000 description 2
• 102000004877 Insulin Human genes 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
• 102000043131 MHC class II family Human genes 0.000 description 2
• 108091054438 MHC class II family Proteins 0.000 description 2
• 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
• 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
• 102000003792 Metallothionein Human genes 0.000 description 2
• 108090000157 Metallothionein Proteins 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 description 2
• 102100023616 Neural cell adhesion molecule L1-like protein Human genes 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• 108010071690 Prealbumin Proteins 0.000 description 2
• 102000007584 Prealbumin Human genes 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 230000006819 RNA synthesis Effects 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 108091028664 Ribonucleotide Proteins 0.000 description 2
• 238000012300 Sequence Analysis Methods 0.000 description 2
• 102000054727 Serum Amyloid A Human genes 0.000 description 2
• 108700028909 Serum Amyloid A Proteins 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 239000012505 Superdex™ Substances 0.000 description 2
• 108700026226 TATA Box Proteins 0.000 description 2
• 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 108090000631 Trypsin Proteins 0.000 description 2
• 102000004142 Trypsin Human genes 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• 241000700618 Vaccinia virus Species 0.000 description 2
• 208000036142 Viral infection Diseases 0.000 description 2
• TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 230000033289 adaptive immune response Effects 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 239000003708 ampul Substances 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 238000006243 chemical reaction Methods 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 239000003593 chromogenic compound Substances 0.000 description 2
• 238000012875 competitive assay Methods 0.000 description 2
• 230000009137 competitive binding Effects 0.000 description 2
• 238000004163 cytometry Methods 0.000 description 2
• 238000013480 data collection Methods 0.000 description 2
• 239000005547 deoxyribonucleotide Substances 0.000 description 2
• 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• 238000010586 diagram Methods 0.000 description 2
• 238000009792 diffusion process Methods 0.000 description 2
• 230000029087 digestion Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 2
• 238000010494 dissociation reaction Methods 0.000 description 2
• 230000005593 dissociations Effects 0.000 description 2
• 125000002228 disulfide group Chemical group 0.000 description 2
• 239000006196 drop Substances 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• RDYMFSUJUZBWLH-UHFFFAOYSA-N endosulfan Chemical compound C12COS(=O)OCC2C2(Cl)C(Cl)=C(Cl)C1(Cl)C2(Cl)Cl RDYMFSUJUZBWLH-UHFFFAOYSA-N 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 238000001502 gel electrophoresis Methods 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 108010017007 glucose-regulated proteins Proteins 0.000 description 2
• 150000004676 glycans Chemical class 0.000 description 2
• 125000001475 halogen functional group Chemical group 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 210000004408 hybridoma Anatomy 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 229910052739 hydrogen Inorganic materials 0.000 description 2
• 150000004679 hydroxides Chemical class 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
• 230000003100 immobilizing effect Effects 0.000 description 2
• 102000018358 immunoglobulin Human genes 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 229940125396 insulin Drugs 0.000 description 2
• 238000001361 intraarterial administration Methods 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
• 210000003292 kidney cell Anatomy 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 210000004962 mammalian cell Anatomy 0.000 description 2
• 239000003550 marker Substances 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• 238000006386 neutralization reaction Methods 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000006179 pH buffering agent Substances 0.000 description 2
• 230000007918 pathogenicity Effects 0.000 description 2
• 102000013415 peroxidase activity proteins Human genes 0.000 description 2
• 108040007629 peroxidase activity proteins Proteins 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 239000008055 phosphate buffer solution Substances 0.000 description 2
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 229920001451 polypropylene glycol Polymers 0.000 description 2
• 229920001282 polysaccharide Polymers 0.000 description 2
• 239000005017 polysaccharide Substances 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
• 229960004919 procaine Drugs 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 230000006337 proteolytic cleavage Effects 0.000 description 2
• 238000011002 quantification Methods 0.000 description 2
• 230000008707 rearrangement Effects 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
• 230000000241 respiratory effect Effects 0.000 description 2
• 239000002336 ribonucleotide Substances 0.000 description 2
• 125000002652 ribonucleotide group Chemical group 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 238000001179 sorption measurement Methods 0.000 description 2
• 230000004936 stimulating effect Effects 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 150000005846 sugar alcohols Chemical class 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
• 230000002103 transcriptional effect Effects 0.000 description 2
• 230000001052 transient effect Effects 0.000 description 2
• 238000013519 translation Methods 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 239000012588 trypsin Substances 0.000 description 2
• 238000002255 vaccination Methods 0.000 description 2
• 230000007502 viral entry Effects 0.000 description 2
• 230000009385 viral infection Effects 0.000 description 2
• 239000013603 viral vector Substances 0.000 description 2
• 238000002424 x-ray crystallography Methods 0.000 description 2
• 239000000811 xylitol Substances 0.000 description 2
• 235000010447 xylitol Nutrition 0.000 description 2
• HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
• 229960002675 xylitol Drugs 0.000 description 2
• HDTRYLNUVZCQOY-UHFFFAOYSA-N &alpha;-D-glucopyranosyl-&alpha;-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
• WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
• LUAHEUHBAZYUOI-KVXMBEGHSA-N (2s,3r,4r,5r)-4-[(2r,3r,4r,5s,6r)-5-[(2r,3r,4r,5s,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexane-1,2,3,5,6-pentol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O[C@@H]([C@H](O)[C@@H](O)CO)[C@H](O)CO)O[C@H](CO)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@@H](CO)O1 LUAHEUHBAZYUOI-KVXMBEGHSA-N 0.000 description 1
• BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
• QGVQZRDQPDLHHV-DPAQBDIFSA-N (3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene-3-thiol Chemical compound C1C=C2C[C@@H](S)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 QGVQZRDQPDLHHV-DPAQBDIFSA-N 0.000 description 1
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical class C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
• PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
• NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
• SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
• TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
• UHUHBFMZVCOEOV-UHFFFAOYSA-N 1h-imidazo[4,5-c]pyridin-4-amine Chemical compound NC1=NC=CC2=C1N=CN2 UHUHBFMZVCOEOV-UHFFFAOYSA-N 0.000 description 1
• VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
• QSHACTSJHMKXTE-UHFFFAOYSA-N 2-(2-aminopropyl)-7h-purin-6-amine Chemical compound CC(N)CC1=NC(N)=C2NC=NC2=N1 QSHACTSJHMKXTE-UHFFFAOYSA-N 0.000 description 1
• JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 description 1
• WKMPTBDYDNUJLF-UHFFFAOYSA-N 2-fluoroadenine Chemical compound NC1=NC(F)=NC2=C1N=CN2 WKMPTBDYDNUJLF-UHFFFAOYSA-N 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• 108700022172 2019-nCoV Vaccine mRNA-1273 Proteins 0.000 description 1
• 108020005345 3' Untranslated Regions Proteins 0.000 description 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• 108020003589 5' Untranslated Regions Proteins 0.000 description 1
• AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 description 1
• ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 description 1
• UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 description 1
• KXBCLNRMQPRVTP-UHFFFAOYSA-N 6-amino-1,5-dihydroimidazo[4,5-c]pyridin-4-one Chemical compound O=C1NC(N)=CC2=C1N=CN2 KXBCLNRMQPRVTP-UHFFFAOYSA-N 0.000 description 1
• DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 1
• QNNARSZPGNJZIX-UHFFFAOYSA-N 6-amino-5-prop-1-ynyl-1h-pyrimidin-2-one Chemical compound CC#CC1=CNC(=O)N=C1N QNNARSZPGNJZIX-UHFFFAOYSA-N 0.000 description 1
• XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
• NJBMMMJOXRZENQ-UHFFFAOYSA-N 6H-pyrrolo[2,3-f]quinoline Chemical compound c1cc2ccc3[nH]cccc3c2n1 NJBMMMJOXRZENQ-UHFFFAOYSA-N 0.000 description 1
• LOSIULRWFAEMFL-UHFFFAOYSA-N 7-deazaguanine Chemical compound O=C1NC(N)=NC2=C1CC=N2 LOSIULRWFAEMFL-UHFFFAOYSA-N 0.000 description 1
• HRYKDUPGBWLLHO-UHFFFAOYSA-N 8-azaadenine Chemical compound NC1=NC=NC2=NNN=C12 HRYKDUPGBWLLHO-UHFFFAOYSA-N 0.000 description 1
• LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 description 1
• 229960005508 8-azaguanine Drugs 0.000 description 1
• 101710177847 Actin, muscle Proteins 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
• 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 102000009027 Albumins Human genes 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 240000000662 Anethum graveolens Species 0.000 description 1
• 238000012935 Averaging Methods 0.000 description 1
• 238000011725 BALB/c mouse Methods 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 206010006448 Bronchiolitis Diseases 0.000 description 1
• YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
• 241001678559 COVID-19 virus Species 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 239000004380 Cholic acid Substances 0.000 description 1
• 108010022452 Collagen Type I Proteins 0.000 description 1
• 102000012422 Collagen Type I Human genes 0.000 description 1
• 102000029816 Collagenase Human genes 0.000 description 1
• 108060005980 Collagenase Proteins 0.000 description 1
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
• 241000711573 Coronaviridae Species 0.000 description 1
• 241000557626 Corvus corax Species 0.000 description 1
• 102000004420 Creatine Kinase Human genes 0.000 description 1
• 108010042126 Creatine kinase Proteins 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 description 1
• OXQKEKGBFMQTML-UHFFFAOYSA-N D-glycero-D-gluco-heptitol Natural products OCC(O)C(O)C(O)C(O)C(O)CO OXQKEKGBFMQTML-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-ZXXMMSQZSA-N D-iditol Chemical compound OC[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-ZXXMMSQZSA-N 0.000 description 1
• HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
• UNXHWFMMPAWVPI-QWWZWVQMSA-N D-threitol Chemical compound OC[C@@H](O)[C@H](O)CO UNXHWFMMPAWVPI-QWWZWVQMSA-N 0.000 description 1
• 102000016559 DNA Primase Human genes 0.000 description 1
• 108010092681 DNA Primase Proteins 0.000 description 1
• 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
• 238000001712 DNA sequencing Methods 0.000 description 1
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
• 102000016911 Deoxyribonucleases Human genes 0.000 description 1
• 108010053770 Deoxyribonucleases Proteins 0.000 description 1
• 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
• 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 1
• 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 1
• 102100039328 Endoplasmin Human genes 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 239000004386 Erythritol Substances 0.000 description 1
• 101710108755 Extracellular serine protease Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 101710189104 Fibritin Proteins 0.000 description 1
• 241000711950 Filoviridae Species 0.000 description 1
• 229930091371 Fructose Natural products 0.000 description 1
• 239000005715 Fructose Substances 0.000 description 1
• RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• 241000713813 Gibbon ape leukemia virus Species 0.000 description 1
• 239000004366 Glucose oxidase Substances 0.000 description 1
• 108010015776 Glucose oxidase Proteins 0.000 description 1
• JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
• 108010062347 HLA-DQ Antigens Proteins 0.000 description 1
• 108010067802 HLA-DR alpha-Chains Proteins 0.000 description 1
• 101150112743 HSPA5 gene Proteins 0.000 description 1
• 241000700721 Hepatitis B virus Species 0.000 description 1
• SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
• 108010033040 Histones Proteins 0.000 description 1
• 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 description 1
• 108010000521 Human Growth Hormone Proteins 0.000 description 1
• 239000000854 Human Growth Hormone Substances 0.000 description 1
• 241000598171 Human adenovirus sp. Species 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 241000711920 Human orthopneumovirus Species 0.000 description 1
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
• 108700002232 Immediate-Early Genes Proteins 0.000 description 1
• 206010061598 Immunodeficiency Diseases 0.000 description 1
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
• UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
• 102000000588 Interleukin-2 Human genes 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
• 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
• 102100027612 Kallikrein-11 Human genes 0.000 description 1
• YINZYTTZHLPWBO-UHFFFAOYSA-N Kifunensine Natural products COC1C(O)C(O)C(O)C2NC(=O)C(=O)N12 YINZYTTZHLPWBO-UHFFFAOYSA-N 0.000 description 1
• SKCKOFZKJLZSFA-UHFFFAOYSA-N L-Gulomethylit Natural products CC(O)C(O)C(O)C(O)CO SKCKOFZKJLZSFA-UHFFFAOYSA-N 0.000 description 1
• LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
• 108010059343 MM Form Creatine Kinase Proteins 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• 238000006845 Michael addition reaction Methods 0.000 description 1
• 229940026207 Moderna COVID-19 vaccine Drugs 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 102000008300 Mutant Proteins Human genes 0.000 description 1
• 108010021466 Mutant Proteins Proteins 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
• 101710163270 Nuclease Proteins 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• 108700005081 Overlapping Genes Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 108010067372 Pancreatic elastase Proteins 0.000 description 1
• 102000016387 Pancreatic elastase Human genes 0.000 description 1
• 241001631646 Papillomaviridae Species 0.000 description 1
• 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
• 241000701945 Parvoviridae Species 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 108091093037 Peptide nucleic acid Proteins 0.000 description 1
• 241000009328 Perro Species 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
• 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 229940096437 Protein S Drugs 0.000 description 1
• 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 description 1
• 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
• 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
• KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 108091034057 RNA (poly(A)) Proteins 0.000 description 1
• 102000009572 RNA Polymerase II Human genes 0.000 description 1
• 108010009460 RNA Polymerase II Proteins 0.000 description 1
• MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
• 101000868151 Rattus norvegicus Somatotropin Proteins 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 208000035415 Reinfection Diseases 0.000 description 1
• 102000009661 Repressor Proteins Human genes 0.000 description 1
• 108010034634 Repressor Proteins Proteins 0.000 description 1
• 208000018569 Respiratory Tract disease Diseases 0.000 description 1
• JVWLUVNSQYXYBE-UHFFFAOYSA-N Ribitol Natural products OCC(C)C(O)C(O)CO JVWLUVNSQYXYBE-UHFFFAOYSA-N 0.000 description 1
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
• 241000714474 Rous sarcoma virus Species 0.000 description 1
• WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
• 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• 101710198474 Spike protein Proteins 0.000 description 1
• 229930182558 Sterol Natural products 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 108091008874 T cell receptors Proteins 0.000 description 1
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 102000006601 Thymidine Kinase Human genes 0.000 description 1
• 108020004440 Thymidine kinase Proteins 0.000 description 1
• 101710195626 Transcriptional activator protein Proteins 0.000 description 1
• 102100031989 Transmembrane protease serine 2 Human genes 0.000 description 1
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
• 102000013394 Troponin I Human genes 0.000 description 1
• 108010065729 Troponin I Proteins 0.000 description 1
• 101710152431 Trypsin-like protease Proteins 0.000 description 1
• 206010053614 Type III immune complex mediated reaction Diseases 0.000 description 1
• MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
• 108010046334 Urease Proteins 0.000 description 1
• 108700005077 Viral Genes Proteins 0.000 description 1
• RLXCFCYWFYXTON-JTTSDREOSA-N [(3S,8S,9S,10R,13S,14S,17R)-3-hydroxy-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-16-yl] N-hexylcarbamate Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(OC(=O)NCCCCCC)[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 RLXCFCYWFYXTON-JTTSDREOSA-N 0.000 description 1
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
• 238000000367 ab initio method Methods 0.000 description 1
• XVIYCJDWYLJQBG-UHFFFAOYSA-N acetic acid;adamantane Chemical compound CC(O)=O.C1C(C2)CC3CC1CC2C3 XVIYCJDWYLJQBG-UHFFFAOYSA-N 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 230000003044 adaptive effect Effects 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000002877 alkyl aryl group Chemical group 0.000 description 1
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
• HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
• 229940003025 amerge Drugs 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 230000005875 antibody response Effects 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 238000000149 argon plasma sintering Methods 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 230000003190 augmentative effect Effects 0.000 description 1
• OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
• 239000003855 balanced salt solution Substances 0.000 description 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 239000013060 biological fluid Substances 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 239000011449 brick Substances 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 210000000234 capsid Anatomy 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000005018 casein Substances 0.000 description 1
• BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
• 235000021240 caseins Nutrition 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 235000019994 cava Nutrition 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000032823 cell division Effects 0.000 description 1
• 210000003855 cell nucleus Anatomy 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 230000004700 cellular uptake Effects 0.000 description 1
• 229940106189 ceramide Drugs 0.000 description 1
• ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
• 235000019416 cholic acid Nutrition 0.000 description 1
• 229960002471 cholic acid Drugs 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 239000008395 clarifying agent Substances 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 230000006957 competitive inhibition Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 239000000356 contaminant Substances 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
• 229940124446 critical care medicine Drugs 0.000 description 1
• 239000002577 cryoprotective agent Substances 0.000 description 1
• 125000001651 cyanato group Chemical group [*]OC#N 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 229960003067 cystine Drugs 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 230000000120 cytopathologic effect Effects 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000007402 cytotoxic response Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 239000000412 dendrimer Substances 0.000 description 1
• 229920000736 dendritic polymer Polymers 0.000 description 1
• KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000001687 destabilization Effects 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 150000001982 diacylglycerols Chemical class 0.000 description 1
• 125000005265 dialkylamine group Chemical group 0.000 description 1
• 150000001985 dialkylglycerols Chemical class 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
• PGUYAANYCROBRT-UHFFFAOYSA-N dihydroxy-selanyl-selanylidene-lambda5-phosphane Chemical compound OP(O)([SeH])=[Se] PGUYAANYCROBRT-UHFFFAOYSA-N 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
• MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 150000002016 disaccharides Chemical class 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 229910000397 disodium phosphate Inorganic materials 0.000 description 1
• 235000019800 disodium phosphate Nutrition 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 229940000406 drug candidate Drugs 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 239000013583 drug formulation Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 241001493065 dsRNA viruses Species 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 238000001493 electron microscopy Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000008393 encapsulating agent Substances 0.000 description 1
• 229940009714 erythritol Drugs 0.000 description 1
• 235000019414 erythritol Nutrition 0.000 description 1
• UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• XJRPTMORGOIMMI-UHFFFAOYSA-N ethyl 2-amino-4-(trifluoromethyl)-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(N)=NC=1C(F)(F)F XJRPTMORGOIMMI-UHFFFAOYSA-N 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 210000003608 fece Anatomy 0.000 description 1
• 235000013312 flour Nutrition 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• SKCKOFZKJLZSFA-FSIIMWSLSA-N fucitol Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO SKCKOFZKJLZSFA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 108010074605 gamma-Globulins Proteins 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 231100000734 genotoxic potential Toxicity 0.000 description 1
• 229940116332 glucose oxidase Drugs 0.000 description 1
• 235000019420 glucose oxidase Nutrition 0.000 description 1
• 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 125000003827 glycol group Chemical group 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 101150028578 grp78 gene Proteins 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000008642 heat stress Effects 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• 239000012145 high-salt buffer Substances 0.000 description 1
• 230000006801 homologous recombination Effects 0.000 description 1
• 238000002744 homologous recombination Methods 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 210000003917 human chromosome Anatomy 0.000 description 1
• 108700023453 human respiratory syncytial virus F Proteins 0.000 description 1
• 235000011167 hydrochloric acid Nutrition 0.000 description 1
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 230000016178 immune complex formation Effects 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 238000003119 immunoblot Methods 0.000 description 1
• 229940127121 immunoconjugate Drugs 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 238000013115 immunohistochemical detection Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 238000009776 industrial production Methods 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
• 229960000367 inositol Drugs 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 230000009878 intermolecular interaction Effects 0.000 description 1
• 230000008863 intramolecular interaction Effects 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 230000002601 intratumoral effect Effects 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 239000000905 isomalt Substances 0.000 description 1
• 235000010439 isomalt Nutrition 0.000 description 1
• HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• OIURYJWYVIAOCW-VFUOTHLCSA-N kifunensine Chemical compound OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H]2NC(=O)C(=O)N12 OIURYJWYVIAOCW-VFUOTHLCSA-N 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000000832 lactitol Substances 0.000 description 1
• 235000010448 lactitol Nutrition 0.000 description 1
• VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
• 229960003451 lactitol Drugs 0.000 description 1
• 125000003473 lipid group Chemical group 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 239000000845 maltitol Substances 0.000 description 1
• 235000010449 maltitol Nutrition 0.000 description 1
• VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
• 229940035436 maltitol Drugs 0.000 description 1
• 238000013178 mathematical model Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 238000010297 mechanical methods and process Methods 0.000 description 1
• 238000005399 mechanical ventilation Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 210000001806 memory b lymphocyte Anatomy 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 230000020654 modulation by virus of host translation Effects 0.000 description 1
• 239000002991 molded plastic Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• 235000019796 monopotassium phosphate Nutrition 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 210000000663 muscle cell Anatomy 0.000 description 1
• 238000002703 mutagenesis Methods 0.000 description 1
• 231100000350 mutagenesis Toxicity 0.000 description 1
• AMKVXSZCKVJAGH-UHFFFAOYSA-N naratriptan Chemical compound C12=CC(CCS(=O)(=O)NC)=CC=C2NC=C1C1CCN(C)CC1 AMKVXSZCKVJAGH-UHFFFAOYSA-N 0.000 description 1
• 239000007923 nasal drop Substances 0.000 description 1
• 229940100662 nasal drops Drugs 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 244000309711 non-enveloped viruses Species 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• 239000006174 pH buffer Substances 0.000 description 1
• 238000012856 packing Methods 0.000 description 1
• 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• ONTNXMBMXUNDBF-UHFFFAOYSA-N pentatriacontane-17,18,19-triol Chemical compound CCCCCCCCCCCCCCCCC(O)C(O)C(O)CCCCCCCCCCCCCCCC ONTNXMBMXUNDBF-UHFFFAOYSA-N 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 229950000688 phenothiazine Drugs 0.000 description 1
• 150000002991 phenoxazines Chemical class 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
• PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical compound NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
• 235000011007 phosphoric acid Nutrition 0.000 description 1
• 150000003016 phosphoric acids Chemical class 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 229920001993 poloxamer 188 Polymers 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 229920000728 polyester Polymers 0.000 description 1
• 108010094020 polyglycine Proteins 0.000 description 1
• 229920000232 polyglycine polymer Polymers 0.000 description 1
• 238000003752 polymerase chain reaction Methods 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
• 230000003334 potential effect Effects 0.000 description 1
• 230000001566 pro-viral effect Effects 0.000 description 1
• 150000003148 prolines Chemical class 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 102000021127 protein binding proteins Human genes 0.000 description 1
• 238000000455 protein structure prediction Methods 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• RXTQGIIIYVEHBN-UHFFFAOYSA-N pyrimido[4,5-b]indol-2-one Chemical compound C1=CC=CC2=NC3=NC(=O)N=CC3=C21 RXTQGIIIYVEHBN-UHFFFAOYSA-N 0.000 description 1
• SRBUGYKMBLUTIS-UHFFFAOYSA-N pyrrolo[2,3-d]pyrimidin-2-one Chemical compound O=C1N=CC2=CC=NC2=N1 SRBUGYKMBLUTIS-UHFFFAOYSA-N 0.000 description 1
• 238000003908 quality control method Methods 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
• 230000006798 recombination Effects 0.000 description 1
• 238000005215 recombination Methods 0.000 description 1
• 230000037425 regulation of transcription Effects 0.000 description 1
• 101150066583 rep gene Proteins 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 210000001525 retina Anatomy 0.000 description 1
• HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 1
• 235000009566 rice Nutrition 0.000 description 1
• 102220053804 rs727503299 Human genes 0.000 description 1
• 238000003118 sandwich ELISA Methods 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
• JRPHGDYSKGJTKZ-UHFFFAOYSA-K selenophosphate Chemical compound [O-]P([O-])([O-])=[Se] JRPHGDYSKGJTKZ-UHFFFAOYSA-K 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000013605 shuttle vector Substances 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 235000020183 skimmed milk Nutrition 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000008137 solubility enhancer Substances 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 229940035044 sorbitan monolaurate Drugs 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008227 sterile water for injection Substances 0.000 description 1
• 150000003432 sterols Chemical class 0.000 description 1
• 235000003702 sterols Nutrition 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 238000012916 structural analysis Methods 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000002344 surface layer Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• 125000005309 thioalkoxy group Chemical group 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• 230000005100 tissue tropism Effects 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000005030 transcription termination Effects 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 150000004043 trisaccharides Chemical class 0.000 description 1
• 230000001810 trypsinlike Effects 0.000 description 1
• PBYZMCDFOULPGH-UHFFFAOYSA-N tungstate Chemical compound [O-][W]([O-])(=O)=O PBYZMCDFOULPGH-UHFFFAOYSA-N 0.000 description 1
• 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 108700026220 vif Genes Proteins 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000001429 visible spectrum Methods 0.000 description 1
• OXQKEKGBFMQTML-KVTDHHQDSA-N volemitol Chemical compound OC[C@@H](O)[C@@H](O)C(O)[C@H](O)[C@H](O)CO OXQKEKGBFMQTML-KVTDHHQDSA-N 0.000 description 1
• 229940075420 xanthine Drugs 0.000 description 1